PCT Patent Publication Nos. WO 2008/104978, WO 2009/044392, WO 2011/066475 and WO 2011/084193 to the assignee of the present invention and hereby incorporated by reference in their entirety, disclose nucleic acid sequences and modifications useful in generating dsRNA molecules.
The synthesis of (L)-alpha-threofuranosyl (TNA) phosphoramidites is described in Scheming et al., Helv. Chim. Acta 85:4111-4153 (2002). Attempts by the present inventors to repeat the syntheses described therein for the preparation of cytosine- and adenine-containing TNAs were unsuccessful.
There remains a need for active and effective dsRNA therapeutic agents which exhibit knock down on target activity and/or reduced off target effects.